Genetic Variant SPTLC1:n.*1756-102G>A (chr9-92001508-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000642671.1(SPTLC1):n.*1756-102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,106 control chromosomes in the GnomAD database, including 24,791 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 24787 hom., cov: 32)

Exomes 𝑓: 0.46 ( 4 hom. )

Consequence

SPTLC1
ENST00000642671.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

5 publications found

Variant links:

COSMIC-nc: COSV69733581

Genes affected

SPTLC1 (HGNC:11277): (serine palmitoyltransferase long chain base subunit 1) This gene encodes a member of the class-II pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is the long chain base subunit 1 of serine palmitoyltransferase. Serine palmitoyltransferase converts L-serine and palmitoyl-CoA to 3-oxosphinganine with pyridoxal 5'-phosphate and is the key enzyme in sphingolipid biosynthesis. Mutations in this gene were identified in patients with hereditary sensory neuropathy type 1. Alternatively spliced variants encoding different isoforms have been identified. Pseudogenes of this gene have been defined on chromosomes 1, 6, 10, and 13. [provided by RefSeq, Jul 2013]

SPTLC1 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis 27, juvenile
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
neuropathy, hereditary sensory and autonomic, type 1A
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hereditary sensory and autonomic neuropathy type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPTLC1 links:

LOC107987094 (HGNC:):

LOC107987094 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC107987094	XR_001746834.2 link	n.480-102G>A	intron_variant	Intron 1 of 2
LOC107987094	XR_001746835.2 link	n.480-102G>A	intron_variant	Intron 1 of 3
LOC107987094	XR_001746836.2 link	n.480-102G>A	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000642671.1 link	n.*1756-102G>A		intron_variant	Intron 16 of 16			ENSP00000495764.1		A0A2R8Y763
SPTLC1	ENST00000643599.1 link	n.*1495-102G>A		intron_variant	Intron 13 of 15			ENSP00000494770.1		A0A2R8Y763

Frequencies

GnomAD3 genomes

AF:

0.533

AC:

81004

AN:

151962

Hom.:

24737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.494

Gnomad EAS

AF:

0.436

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.494

GnomAD4 exome

AF:

0.462

AC:

AN:

Hom.:

AF XY:

0.444

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.458

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.533

AC:

81115

AN:

152080

Hom.:

24787

Cov.:

AF XY:

0.533

AC XY:

39658

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.847

AC:

35170

AN:

41514

American (AMR)

AF:

0.568

AC:

8686

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.494

AC:

1714

AN:

3470

East Asian (EAS)

AF:

0.437

AC:

2257

AN:

5164

South Asian (SAS)

AF:

0.448

AC:

2155

AN:

4808

European-Finnish (FIN)

AF:

0.378

AC:

3990

AN:

10562

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.377

AC:

25613

AN:

67960

Other (OTH)

AF:

0.497

AC:

1047

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1647

3293

4940

6586

8233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.439

Hom.:

8870

Bravo

AF:

0.560

Asia WGS

AF:

0.489

AC:

1704

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.85

(source)

DANN

Benign

0.76

PhyloP100

-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over